Assessment of thyrotoxicity using in vitro cell culture systems

The potential thyrotoxic effect of SK&F 93479 (an H2-receptor antagonist), aminoglutethimide (AG) and glutethimide were studied by examining their effects on 125iodide uptake and organification (incorporation into thyroglobulin) in cultured thyroid cells from the pig and rat. These effects were compared with those of positive controls (3-isobutyl-1-methylxanthine (IBMX), methimazole (MTI), propylthiouracil (PTU) and NaClO4). SK&F 93479 had no effect on 125I uptake in rat FRTL-5 cells or on 125I uptake and organification in porcine thyroid cells. In contrast, MTI, PTU and NaClO4 all depressed 125I uptake and organification and IBMX potentiated 125I uptake. It is concluded, therefore, that SK&F 93479 does not increase 125I uptake in rats in vivo by a direct action on the thyroidal iodide trapping mechanism. AG, but not glutethimide, depressed 125I organification by cultured porcine thyrocytes without affecting uptake. These results suggest that AG is thyrotoxic in rats and man probably as a result of its ability to inhibit iodide organification in thyroid cells.